This project is to continue studies of factors regulating the proliferation and differentiation of hematopoietic stem cells and progenitor cells in normal and disease states. Emphasis of study will be directed to two areas: 1) Studies of granulocyte-macrophage colony stimulating activity (GM-CSA) and 2) The differentiation of promyelocytic leukemia cells (HL-60) by retinoic acid. Colony stimulating activity represents a family of glycoproteins necessary for the proliferation and differentiation of granulocyte-macrophage progenitor cells (CFU-GM) in vitro. While many studies have been done with CSA in vitro, there is yet no convincing evidence for its role in vivo. These will include: 1) further purification of spleen cell derived CSA, 2) raising monoclonal antibodies to CSA, 3) prepare large quantities of purified CSA, and 4) determine its role in vivo. Other studies will be directed to the differentiation of HL-60 leukemia cells. These cells can be induced to differentiate to mature appearing neutrophils when exposed to retinoic acid. Recently we observed that a new nucleosomal protein (P-60) appeared during differentiation. Studies will be continued in order to 1) determine the specificity and significance of P60 in cell differentiation, 2) is P60 specific for RA or does it appear with other inducers of differentiation, 3) purification and preparing antibodies to P60, and 4) determine if a retinoic acid binding protein (RABP) is involved in the regulation of HL-60 differentiation.